IgE is the immunoglobulin most commonly known as the main cause of anaphylaxis or, more generally speaking, of the immediate hypersensitivity states, such as asthma, hay fever, atopic dermatitis, and other well-known manifestations of atopic patients. IgE is present in normal individuals at very low concentrations, normally somewhat less than 1 |ig/mL. This concentration may be considerably elevated in patients suffering from one or another form of immediate hypersensitivity, and also in patients with internal parasite infections. This points to a major role as support of anaphylactoid states and suggests a possible role in the defense against parasites, a view that has been seriously reinforced of late.
IgE is a monomer of molecular formula
It may, as all the other Ig subclasses, be expressed as cell-surface or circulating Ig, and it has an elevated carbohydrate content (>10% by weight). The 6 chains have four constant Cd domains, and the molecular weight of IgE averages 180 kDa. IgE does not fix complement and is heat-labile. Its role in driving the immediate hypersensitivity reactions is due to the fixation of circulating IgE antibodies on Fc receptors of very high affinity; FcR^I is located on several cell types, mostly basophils and mast cells. These large cells contain granules that contain a high concentration of pharmacologically active substances, like histamine, neutral proteinases, proteoglycans, and tumor necrosis factor a; (TNFa). Contact of an antigen (here denominated an allergen) with specific IgE fixed to such cells of an atopic patient who has already been sensitized will activate the target cell and release the pharmacologically active substances, thus initiating a large cascade of secondary reactions. Histamine will bind selectively to H1-type receptors and exert various deleterious effects, such as vasodilatation, local exudation, and spasmogenic activity of intestinal, uterine, or bronchial muscles, depending on the localization of the target. TNFa liberated upon mast-cell activation may have a beneficial effect in antimicrobial defense. Other mediators are synthesized as a response to IgE triggering. Those include prostaglandins, PGD2, leukotrienes, and so on, and a large number of cytokines that considerably amplify the response and especially initiate a strong inflammatory reaction. Fixation of IgE on other cell types, like eosinophils, macrophages, or platelets, can also occur through the FceRII, which is of lower affinity than Fce RI, and trigger liberation of many mediators, including free radicals that may be beneficial by helping to fight against pathogens, although most of the effects are quite aggressive for the host tissues.
Discovery of the two main populations of helper T cells, Th1 and Th2, which drive a fine regulation of the immune response through a complex network of cytokines, has opened the way to a reinvestigation of the possibility of modulation of the expression of IgE, which is of prime importance for atopic patients, but also to fight more effectively against parasites, which remain quite elusive pathogens to date. IgE production is essentially driven by cytokines of the Th2 group, particularly interleukin 4, which was shown to favor the class switch to this Ig class.
